Dual anti-platelet therapy (DAPT) reduces cardiovascular events after PCI by more than 80%. However, stent thrombosis can occur in 0.5% to 4% of patients within the first year following PCI, with the majority occurring in the first month. Cayla et al. performed a case-control study using a candidate gene approach – looking in particular at genetic variations previously associated with clopidogrel pharmocogenetics and arterial thrombosis – in order to determine their impact on early stent thrombosis, in addition to established clinical and angiographic factors.
The study was conducted across ten centres in France over a three-year period, and involved 123 patients undergoing PCI who had definite early stent thrombosis and DNA samples available, matched on age and sex with 246 thrombosis-free controls. 23 genetic variants were investigated in 15 different genes, and three were found to be significant: CYP2C19 metabolic status (adjusted odds ratio, 1.99), ABCB1 3435 TT genotype (adjusted OR, 2.16), and ITGB3 PLA2 carriage (adjusted OR, 0.52). Other non genetic independent correlates included acuteness of PCI (adjusted OR, 3.05), complex lesions (American College of Cardiology/American Heart Association type C) (adjusted OR, 2.33), left ventricular function less than 40% (adjusted OR, 2.25), diabetes mellitus (adjusted OR, 1.82), use of proton pump inhibitors (adjusted OR, 2.19), and higher clopidogrel loading doses (adjusted OR, 0.73). A combined clinical and genetic model showed a statistically significant superiority in its ability to predict stent thrombosis compared to a clinical-only model.
In this case-control study three genea (CYP2C19,ABCB1,andITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) were independently associated with early stent thrombosis. Further prospective studies are needed to confirm these associations.
- Cayla G, Hulot J-S, O’Connor SA et al. Clinical, Angiographic, and Genetic Factors Associated With Early Coronary Stent Thrombosis. JAMA 2011; 306: -1765-1774.